EFFECT OF ROUTINE USE OF THERAPY IN SLOWING THE CLINICAL COURSE OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION IN A POPULATION-BASED COHORT

Clinical trials have shown that the prophylactic use of zidovudine and aerosolized pentamidine (or other antibiotics used as prophylaxis aga inst Pneumocystis carinii pneumonia) in acquired immunodeficiency synd rome (AIDS)-free human immunodeficiency virus (HIV)-infected persons d elays the development of AIDS, but the effectiveness of such therapy i n general use in the population still remains largely undocumented. To help answer this question, the authors estimate the effectiveness of this therapy in a population-based cohort of HIV-infected homosexual a nd bisexual men in San Francisco. The authors use a continuous-time Ma rkov process to model the decline of CD4+ T-lymphocytes (T4-cells) mea sured in cells/muliter in HIV-infected persons. The model partitions t he HIV (type 1) infection period into six progressive T4-cell count in tervals (stages), followed by a seventh stage: AIDS diagnosis. The aut hors use maximum likelihood methods to fit the model to the observed t ransitions for 428 HIV-infected men during June 1984 to March 1991, fr om the San Francisco Men's Health Study. Since zidovudine was not wide ly used before 1988, the model has a component that controls for calen dar time-related biases. The fitted model provides statistical estimat es and confidence intervals for measuring therapy effectiveness. The a uthors estimate that prophylactic therapy reduces the progression rate from stage 4 (T4-cell count, 350-499) to stage 5 (T4-cell count, 200- 349) by a factor of 0.26 (95% confidence interval (CI) -0.22 to 0.55); from stage 5 to stage 6 (T4-cell count <200) by a factor of 0.33 (95% CI 0.04-0.54); and from stage 6 to 7 (AIDS) by a factor of 0.62 (95% CI 0.47-0.73). In addition, therapy started by an HIV-infected person in stage 4 is estimated to reduce the risk of developing AIDS by a fac tor of 0.83 (95% CI 0.46-0.94) at 6 months and 0.68 (95% CI 0.35-0.89) at 24 months after entering stage 4. Therapy started by HIV-infected persons in more advanced stages is estimated to reduce the risk of dev eloping AIDS by factors ranging from 0.70 (95% CI 0.39-0.90), early in stage 5, to 0.28 (95% CI 0.14-0.45), late in stage 6. Thus, the proph ylactic use of zidovudine and pentamidine in routine medical care has a strong, consistent, and significant effect in slowing the clinical c ourse of HIV infection in a population-based cohort.